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https://www.readbyqxmd.com/read/29325868/canadian-genome-wide-association-study-and-meta-analysis-confirm-hla-as-a-risk-factor-for-peanut-allergy-independent-of-asthma
#1
Yuka Asai, Aida Eslami, C Dorien van Ginkel, Loubna Akhabir, Ming Wan, David Yin, George Ellis, Moshe Ben-Shoshan, Ingo Marenholz, David Martino, Manuel A Ferreira, Katrina Allen, Bruce Mazer, Hans de Groot, Nicolette W de Jong, Roy Gerth van Wijk, Anthony E J Dubois, Sarah Grosche, Sarah Ashley, Franz Rüschendorf, Birgit Kalb, Kirsten Beyer, Markus M Nöthen, Young-Ae Lee, Rick Chin, Steven Cheuk, Joshua Hoffman, Eric Jorgensen, John S Witte, Ronald B Melles, Xiumei Hong, Xiaobin Wang, Jennie Hui, Arthur W Bill Musk, Michael Hunter, Alan L James, Gerard H Koppelman, Andrew J Sandford, Ann E Clarke, Denise Daley
No abstract text is available yet for this article.
January 8, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29273806/multiancestry-association-study-identifies-new-asthma-risk-loci-that-colocalize-with-immune-cell-enhancer-marks
#2
Florence Demenais, Patricia Margaritte-Jeannin, Kathleen C Barnes, William O C Cookson, Janine Altmüller, Wei Ang, R Graham Barr, Terri H Beaty, Allan B Becker, John Beilby, Hans Bisgaard, Unnur Steina Bjornsdottir, Eugene Bleecker, Klaus Bønnelykke, Dorret I Boomsma, Emmanuelle Bouzigon, Christopher E Brightling, Myriam Brossard, Guy G Brusselle, Esteban Burchard, Kristin M Burkart, Andrew Bush, Moira Chan-Yeung, Kian Fan Chung, Alexessander Couto Alves, John A Curtin, Adnan Custovic, Denise Daley, Johan C de Jongste, Blanca E Del-Rio-Navarro, Kathleen M Donohue, Liesbeth Duijts, Celeste Eng, Johan G Eriksson, Martin Farrall, Yuliya Fedorova, Bjarke Feenstra, Manuel A Ferreira, Maxim B Freidin, Zofia Gajdos, Jim Gauderman, Ulrike Gehring, Frank Geller, Jon Genuneit, Sina A Gharib, Frank Gilliland, Raquel Granell, Penelope E Graves, Daniel F Gudbjartsson, Tari Haahtela, Susan R Heckbert, Dick Heederik, Joachim Heinrich, Markku Heliövaara, John Henderson, Blanca E Himes, Hiroshi Hirose, Joel N Hirschhorn, Albert Hofman, Patrick Holt, Jouke Hottenga, Thomas J Hudson, Jennie Hui, Medea Imboden, Vladimir Ivanov, Vincent W V Jaddoe, Alan James, Christer Janson, Marjo-Riitta Jarvelin, Deborah Jarvis, Graham Jones, Ingileif Jonsdottir, Pekka Jousilahti, Michael Kabesch, Mika Kähönen, David B Kantor, Alexandra S Karunas, Elza Khusnutdinova, Gerard H Koppelman, Anita L Kozyrskyj, Eskil Kreiner, Michiaki Kubo, Rajesh Kumar, Ashish Kumar, Mikko Kuokkanen, Lies Lahousse, Tarja Laitinen, Catherine Laprise, Mark Lathrop, Susanne Lau, Young-Ae Lee, Terho Lehtimäki, Sébastien Letort, Albert M Levin, Guo Li, Liming Liang, Laura R Loehr, Stephanie J London, Daan W Loth, Ani Manichaikul, Ingo Marenholz, Fernando J Martinez, Melanie C Matheson, Rasika A Mathias, Kenji Matsumoto, Hamdi Mbarek, Wendy L McArdle, Mads Melbye, Erik Melén, Deborah Meyers, Sven Michel, Hamida Mohamdi, Arthur W Musk, Rachel A Myers, Maartje A E Nieuwenhuis, Emiko Noguchi, George T O'Connor, Ludmila M Ogorodova, Cameron D Palmer, Aarno Palotie, Julie E Park, Craig E Pennell, Göran Pershagen, Alexey Polonikov, Dirkje S Postma, Nicole Probst-Hensch, Valery P Puzyrev, Benjamin A Raby, Olli T Raitakari, Adaikalavan Ramasamy, Stephen S Rich, Colin F Robertson, Isabelle Romieu, Muhammad T Salam, Veikko Salomaa, Vivi Schlünssen, Robert Scott, Polina A Selivanova, Torben Sigsgaard, Angela Simpson, Valérie Siroux, Lewis J Smith, Maria Solodilova, Marie Standl, Kari Stefansson, David P Strachan, Bruno H Stricker, Atsushi Takahashi, Philip J Thompson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Carla M T Tiesler, Dara G Torgerson, Tatsuhiko Tsunoda, André G Uitterlinden, Ralf J P van der Valk, Amaury Vaysse, Sailaja Vedantam, Andrea von Berg, Erika von Mutius, Judith M Vonk, Johannes Waage, Nick J Wareham, Scott T Weiss, Wendy B White, Magnus Wickman, Elisabeth Widén, Gonneke Willemsen, L Keoki Williams, Inge M Wouters, James J Yang, Jing Hua Zhao, Miriam F Moffatt, Carole Ober, Dan L Nicolae
We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases...
January 2018: Nature Genetics
https://www.readbyqxmd.com/read/29212039/comprehensive-mapping-of-pluripotent-stem-cell-metabolism-using-dynamic-genome-scale-network-modeling
#3
Sriram Chandrasekaran, Jin Zhang, Zhen Sun, Li Zhang, Christian A Ross, Yu-Chung Huang, John M Asara, Hu Li, George Q Daley, James J Collins
Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29069550/is-there-merit-in-merit-aid
#4
Roy C Ziegelstein, Charles G Prober, Lloyd B Minor, George Q Daley, Paul B Rothman, Edward M Hundert
In 2016, the average cost of attending medical school (including tuition and fees) in the United States was $253,720 for in-state graduates and $313,897 for out-of-state graduates. Nearly three in four graduates had educational debt, and the median educational debt was $190,000. Average debt..
October 25, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29030101/genome-wide-association-study-and-meta-analysis-in-multiple-populations-identifies-new-loci-for-peanut-allergy-and-establishes-c11orf30-emsy-as-a-genetic-risk-factor-for-food-allergy
#5
Yuka Asai, Aida Eslami, C Dorien van Ginkel, Loubna Akhabir, Ming Wan, George Ellis, Moshe Ben-Shoshan, David Martino, Manuel A Ferreira, Katrina Allen, Bruce Mazer, Hans de Groot, Nicolette W de Jong, Roy N Gerth van Wijk, Anthony E J Dubois, Rick Chin, Steven Cheuk, Joshua Hoffman, Eric Jorgensen, John S Witte, Ronald B Melles, Xiumei Hong, Xiaobin Wang, Jennie Hui, Arthur W Bill Musk, Michael Hunter, Alan L James, Gerard H Koppelman, Andrew J Sandford, Ann E Clarke, Denise Daley
BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously PA loci were identified in FLG and HLA in candidate gene studies, and loci in HLA in a genome-wide association study and meta-analysis. OBJECTIVE: To investigate genetic susceptibility to PA. METHODS: Eight hundred and fifty cases and 926 hyper-controls and >7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population...
October 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28928278/an-interview-with-george-daley
#6
Aidan Maartens
George Daley is Dean of the Faculty of Medicine, Professor of Biological Chemistry and Molecular Pharmacology, and Caroline Shields Walker Professor of Medicine at Harvard Medical School. A former Howard Hughes Medical Institute Investigator and President of the International Society for Stem Cell Research (ISSCR) from 2007-2008, his lab works on the biology and clinical application of stem cells, with a particular focus on hematopoiesis. He was awarded the Public Service Award at the ISSCR 2017 meeting in Boston, where we caught up with him to discuss his move from the lab to the clinic and back again, his quest to derive human hematopoietic stem cells in vitro, and his advocacy for science in uncertain political times...
September 15, 2017: Development
https://www.readbyqxmd.com/read/28686862/making-hscs-on-demand-looking-ahead
#7
(no author information available yet)
George Daley and Shahin Rafii's groups recently generated multilineage, serially engrafting hematopoietic stem cells (HSCs) from human pluripotent stem cells and endothelial cells, respectively, achieving an important research milestone for the field. We asked some experts in the field to reflect on the broader implications of these findings.
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28619647/using-crispr-cas9-to-generate-gene-corrected-autologous-ipscs-for-the-treatment-of-inherited-retinal-degeneration
#8
Erin R Burnight, Manav Gupta, Luke A Wiley, Kristin R Anfinson, Audrey Tran, Robinson Triboulet, Jeremy M Hoffmann, Darcey L Klaahsen, Jeaneen L Andorf, Chunhua Jiao, Elliott H Sohn, Malavika K Adur, Jason W Ross, Robert F Mullins, George Q Daley, Thorsten M Schlaeger, Edwin M Stone, Budd A Tucker
Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function...
September 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28531208/phylogenetic-analysis-of-emergent-streptococcus-pneumoniae-serotype-22f-causing-invasive-pneumococcal-disease-using-whole-genome-sequencing
#9
Walter H B Demczuk, Irene Martin, Linda Hoang, Paul Van Caeseele, Brigitte Lefebvre, Greg Horsman, David Haldane, Jonathan Gubbay, Sam Ratnam, Gregory German, Jennifer Daley Bernier, Lori Strudwick, Allison McGeer, George G Zhanel, Gary Van Domselaar, Morag Graham, Michael R Mulvey
Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015...
2017: PloS One
https://www.readbyqxmd.com/read/28514439/haematopoietic-stem-and-progenitor-cells-from-human-pluripotent-stem-cells
#10
Ryohichi Sugimura, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz da Rocha, Yi-Fen Lu, Jeremy A Goettel, Erik Serrao, R Grant Rowe, Mohan Malleshaiah, Irene Wong, Patricia Sousa, Ted N Zhu, Andrea Ditadi, Gordon Keller, Alan N Engelman, Scott B Snapper, Sergei Doulatov, George Q Daley
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28442553/nlrp3-signaling-drives-macrophage-induced-adaptive-immune-suppression-in-pancreatic-carcinoma
#11
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Gautam S D Balasubramania Pandian, Shivraj Savadkar, Ki Buom Lee, Alejandro Torres-Hernandez, Berk Aykut, Brian Diskin, Wei Wang, Mohammad S Farooq, Arif I Mahmud, Gregor Werba, Eduardo J Morales, Sarah Lall, Benjamin J Wadowski, Amanda G Rubin, Matthew E Berman, Rajkishen Narayanan, Mautin Hundeyin, George Miller
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4(+) T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8(+) T cell activation...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28429768/reassembling-embryos-in-vitro-from-component-stem-cells
#12
Caroline Kubaczka, George Q Daley
Researchers at the University of Cambridge, UK have succeeded in reconstructing mouse embryos by combining pluripotent embryonic and multipotent trophoblast stem cells in a 3D scaffold; the study from the laboratory of Professor Zernicka-Goetz, recently published in Science, provides a break-through tool to probe early mammalian development outside the uterus. Achieving a similar feat with human cells might necessitate reconsideration of the 14-day rule as a limitation of such research.
August 2017: Cell Research
https://www.readbyqxmd.com/read/28394331/dectin-1-activation-on-macrophages-by-galectin-9-promotes-pancreatic-carcinoma-and-peritumoral-immune-tolerance
#13
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Atsuo Ochi, Daniel W Heindel, Ki Buom Lee, Constantinos P Zambirinis, Gautam Sd Balasubramania Pandian, Shivraj Savadkar, Alejandro Torres-Hernandez, Shruti Nayak, Ding Wang, Mautin Hundeyin, Brian Diskin, Berk Aykut, Gregor Werba, Rocky M Barilla, Robert Rodriguez, Steven Chang, Lawrence Gardner, Lara K Mahal, Beatrix Ueberheide, George Miller
The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined. Furthermore, non-pathogen-derived ligands for dectin 1 have not been characterized. We found that dectin 1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA)...
May 2017: Nature Medicine
https://www.readbyqxmd.com/read/28350984/autophagy-it-s-in-your-blood
#14
COMMENT
Sergei Doulatov, George Q Daley
Autophagy, a central pathway for cellular homeostasis, plays diverse roles in development, cancer, aging, and neurodegeneration. In a new report in Nature, Ho et al. (2017) show that autophagy is essential for maintaining the replicative quiescence of hematopoietic stem cells throughout life by limiting the number of active mitochondria.
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28345379/the-role-of-%C3%AE-%C3%AE-t-cells-in-pancreatic-cancer-what-could-this-mean-for-the-clinic
#15
Donnele Daley, George Miller
No abstract text is available yet for this article.
April 11, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28296612/polar-extremes-in-the-clinical-use-of-stem-cells
#16
George Q Daley
The U.S. biotechnology and pharmaceutical industries arguably lead the world in innovation while operating under stringent regulations set by the Food and Drug Administration (FDA). Although flexible pathways exist to accelerate the development or approval of treatments for serious illnesses or..
March 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28272977/signaling-through-rna-binding-proteins-as-a-cell-fate-regulatory-mechanism
#17
Kaloyan M Tsanov, George Q Daley
No abstract text is available yet for this article.
April 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28179501/drug-discovery-for-diamond-blackfan-anemia-using-reprogrammed-hematopoietic-progenitors
#18
Sergei Doulatov, Linda T Vo, Elizabeth R Macari, Lara Wahlster, Melissa A Kinney, Alison M Taylor, Jessica Barragan, Manav Gupta, Katherine McGrath, Hsiang-Ying Lee, Jessica M Humphries, Alex DeVine, Anupama Narla, Blanche P Alter, Alan H Beggs, Suneet Agarwal, Benjamin L Ebert, Hanna T Gazda, Harvey F Lodish, Colin A Sieff, Thorsten M Schlaeger, Leonard I Zon, George Q Daley
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients...
February 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077678/disruptive-reproductive-technologies
#19
REVIEW
I Glenn Cohen, George Q Daley, Eli Y Adashi
In vitro gametogenesis raises new possibilities for reproductive and regenerative medicine as well as vexing policy challenges.
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28009288/engineered-murine-hscs-reconstitute-multi-lineage-hematopoiesis-and-adaptive-immunity
#20
Yi-Fen Lu, Patrick Cahan, Samantha Ross, Julie Sahalie, Patricia M Sousa, Brandon K Hadland, Wenqing Cai, Erik Serrao, Alan N Engelman, Irwin D Bernstein, George Q Daley
Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs) could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients...
December 20, 2016: Cell Reports
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